Classical cannabinoids such as the marijuana derived cannabinoid (CB) delta9-tetrahydro-cannabinol, (delta9-THC) produce their pharmacological effects via interaction with specific cannabinoid receptors in the body. So far, two cannabinoid receptors have been characterized: CB1, a receptor found in the mammalian brain and peripheral tissues and CB2, a receptor found predominantly in the peripheral tissues. There is considerable interest in developing cannabinoid analogs that have selective CB2 agonistic activity since it is believed high selectivity for CB2 receptor may offer avenues for harnessing the beneficial effect of CB receptor agonists while avoiding the central adverse events seen with cannabinoid structures (see e.g. Expert Opin. Investig. Drugs (2007) 16(7):951-965).
In general, CB2 receptor agonists are found to be useful for the treatment of a variety of diseases, including inflammatory pain, nociceptive pain, neuropathic pain, fibromyalgia, chronic low back pain, visceral pain, rheumatoid arthritis, Crohn's disease, ulcerative colitis, asthma, dermatitis, seasonal allergic rhinitis, gastroesophageal reflux disease (GERD), constipation, diarrhea, functional gastrointestinal disorder, irritable bowel syndrome (IBS), cutaneous T cell lymphoma, multiple sclerosis, osteoarthritis, psoriasis, systemic lupus erythematosus, diabetes, glaucoma, osteoporosis, glomerulonephritis, renal ischemia, nephritis, hepatitis, cerebral stroke, vasculitis, myocardial infarction, cerebral ischemia, reversible airway obstruction, adult respiratory disease syndrome, chronic obstructive pulmonary disease (COPD), cryptogenic fibrosing alveolitis and bronchitis (see J Pharmacol Exp Ther. 2004 February; 308(2):446-53; Proc Natl Acad Sci USA. 2003 Sep. 2; 100(18):10529-33; Br J Pharmacol. 2004 August; 142(8): 1247-54).
WO 2006/048754, WO 2007/102059, WO 2008/003665, and WO 2008/119694 disclose sulfonyl compounds as CB2 agonists. WO 2006/048754 formally discloses a heterocyclyl group on the sulfonyl group. WO 2007/102059 is not disclosed heterocyclic moiety on the sulfonyl group. WO 2008/003665 and WO 2008/119694 only disclose aryl or heteroaryl moiety on the sulfonyl group.